In past reporting periods, we procured a series of primary endometrial carcinosarcomas and paired non-tumor tissues through the Cooperative Human Tissue Network, which is supported by the National Cancer Institute. During the current reporting period, we: 1. Subjected a subset of the MMMT tumor-normal pairs to whole exome sequencing at the NIH Intramural Sequencing Center. 2. Curated and filtered the exome sequence data to distinguish germline variants (present in both tumor and normal DNAs) from somatic variants (present exclusively in the tumor DNA). 3. Subjected the somatic variants to orthogonal validation, using Sanger sequencing and/or mass spectrometry, to distinguish true somatic mutations from false-positive calls. 4. Prioritized a subset of nonsynonymously, somatically mutated genes for further analysis in a mutation prevalence screen. In the incoming reporting period we plan to: 1. Perform the mutation prevalence screen. In this screen we will sequence the subset of prioritized genes, which we hypothesize are likely to be causal cancer genes, from an independent cohort of MMMTs. This will allow us to precisely determine the mutation rate, mutation frequency, and mutation spectrum of these genes in MMMTs. 2. Next, we will use statistical methods to determine whether any of the genes in the mutation prevalence screen are so-called significantly-mutated genes, i.e. whether they are mutated at a statistically significantly higher rate than the background mutation rate for MMMTs. We hypothesize that significantly-mutated genes are likely to be causal cancer genes that contribute to the development of MMMTs. 3. We will also analyze the whole exome sequence data to identify somatic copy number alterations in MMMTs.